DB-OTO Gene Therapy for Inherited Deafness
Vassili Valayannopoulos, Manohar Bance, Daniela Carvalho, John H. Greinwald, Steven Harvey, Akira Ishiyama, Evie C. Landry, Hubert Löwenheim, Lawrence R. Lustig, Manuel Manrique, Robert Nash, Rubén Polo, Cedric V. Pritchett, Jay T. Rubinstein, A. Eliot Shearer, Ignacio del Castillo, Jeffery J. Anderson, C. Eduardo Corrales, Tera Quigley, William J. Riggs, Peter Weber, G. S. Wilson, Susan C. Irvin, Hazem E. Hassan, Yanping Chen, Rong Liu, Meghan C. Drummond, Leah R. Sabin, Bret J. Musser, George D. Yancopoulos, Christos A. Kyratsous, Gary Herman, Aris Baras, Jonathon P. Whitton
Abstract
BACKGROUND: complementary DNA (encoding otoferlin) regulated by a hair cell-specific promoter. METHODS: vector genomes per ear) in one or both ears. The primary efficacy end point was an average threshold on behavioral pure-tone audiometry (PTA) at week 24 of 70 dB HL or less, a clinical standard that generally avoids cochlear implantation and enables natural acoustic hearing. A key secondary end point was the presence of an auditory brain-stem response to a click stimulus at a threshold at or below 90 dB normalized hearing level (db nHL) at week 24. Safety assessments included adverse events, laboratory results, and vestibular testing. RESULTS: for both end points). Six participants could hear soft speech without assistive devices, and 3 had average normal hearing sensitivity. A total of 67 adverse events occurred or worsened during or after treatment, none of which led to discontinued participation in the study. CONCLUSIONS: -related deafness, enabling natural acoustic hearing and normalizing hearing sensitivity in 3 of 12 treated patients. (Funded by Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT05788536.).